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Fig. 2
Modulation of the cell cycle by proteins in the virus particle and immediate early proteins.
The tegument proteins pUL69 and pp71 can exert their effects on the cell cycle upon entry of the
virus particle into the cell. pUL69 causes accumulation of cells in G
1
phase, while pp71 targets
the hypophosphorylated forms of the Rb family of proteins (Rb, p107, p130) and the transcrip-
tional inhibitor Daxx for proteasome-mediated degradation. This degradation of the Rb proteins
along with their viral-mediated hyperphosphorylation lead to the release of the E2F/DP transcrip-
tion factors, which activate many genes involved in DNA replication and promotes S phase. The
IE1 protein blocks the activity of p130/p107, and IE2 interferes with at least some functions of Rb
and p53. Both IE proteins can prevent cells from passage through S phase
time (Kalejta and Shenk 2003) . These results suggest that pp71 delivered to cells
as part of the incoming virus particles may stimulate the cell cycle at the beginning
of the infection before IE gene expression. The finding that pp71 also interacts with
ND10-associated transcription repressor Daxx and promotes its proteasome-
mediated degradation suggests an additional function for pp71 in initiating viral
transcription at ND10 sites (Hofmann et al. 2002; Ishov et al. 2002; Marshall et al.
2002; Cantrell and Bresnahan 2005; Saffert and Kalejta 2006).
Immediate Early Protein 1
HCMV encodes two IE proteins, IE1-72 and IE2-86, that have been shown to inter-
fere with cell cycle progression in heterologous systems in the absence of infection.
Transient expression of IE1-72 in asynchronously cycling cells stimulates their
accumulation in the S and G
2
/ M phases of the cell cycle (Castillo et al. 2000). One
possible explanation for this result is that it is due to the interaction of IE1-72 with
